Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation

EMBO J. 2007 Aug 8;26(15):3699-708. doi: 10.1038/sj.emboj.7601790. Epub 2007 Jul 12.


MicroRNAs (miRNAs) are potent post-transcriptional regulators of protein coding genes. Patterns of misexpression of miRNAs in cancer suggest key functions of miRNAs in tumorigenesis. However, current bioinformatics tools do not entirely support the identification and characterization of the mode of action of such miRNAs. Here, we used a novel functional genetic approach and identified miR-221 and miR-222 (miR-221&222) as potent regulators of p27(Kip1), a cell cycle inhibitor and tumor suppressor. Using miRNA inhibitors, we demonstrate that certain cancer cell lines require high activity of miR-221&222 to maintain low p27(Kip1) levels and continuous proliferation. Interestingly, high levels of miR-221&222 appear in glioblastomas and correlate with low levels of p27(Kip1) protein. Thus, deregulated expression of miR-221&222 promotes cancerous growth by inhibiting the expression of p27(Kip1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cyclin-Dependent Kinase Inhibitor p27 / physiology*
  • Flow Cytometry
  • Humans
  • Mice
  • MicroRNAs / physiology*
  • Neoplasms / pathology*
  • Reverse Transcriptase Polymerase Chain Reaction


  • MicroRNAs
  • Cyclin-Dependent Kinase Inhibitor p27